Current Pharmaceutical Biotechnology - Online First

The most prevalent kind of cancer among women is breast cancer. Consequently, the development of novel, potent medications with fewer adverse effects is required to treat it. Breast cancer is frequently treated clinically with chemotherapy and surgery. However, there are still significant challenges to be addressed in the treatment of breast cancer, including inadequate therapeutic results, inevitable side effects, and the surgical excision of breast tissue. The objective of the study is to develop broccoli extract-based Hydrogel to overcome the challenges in breast cancer treatment.

The developed Hydrogel was characterized by certain techniques to check its stability and drug release abilities. Swelling studies and drug release behavior were checked; the porosity of Hydrogel was checked by SEM EDX Analysis. Furthermore, in vitro studies were done to check the anti-breast cancer activity of the developed Hydrogel.

The hydrogel was a highly porous structure with and compressive modulus, which makes it good for biological use in drug delivery. The in vitro studies showed that, developed Hydrogel inhibits the growth of breast cancer cells (MCF-7) at different concentrations and time intervals of 24 and 48 Hrs and was compatible with the non-cancerous cell line 3T3-L1. The results indicate the tolerability of Hydrogel at the level of cells.

Numerous investigations have demonstrated the anticancer effects of SFN by influencing the various biological processes that tumor cells engage in. In breast cancer cell lines, SFN functions as an HDAC inhibitor and reduces the expression of ER, EGFR, & HER-2 proteins. SFN also triggers apoptosis and cell cycle halt. Both Hydrogel and SFN inhibit the cells growth in MCF-7 breast cancer cells and agree with the previous studies.

In conclusion, we synthesized a hydrogel using broccoli extract to treat breast cancer with better stability, tolerance, and effectiveness through sustained local drug delivery. It was determined that this new hydrogel was a simple and affordable way to accomplish the continuous gene release feature, which would enhance the therapeutic efficacy in anti-cancer treatment while reducing the likelihood of potentially fatal side effects.

In view of the increasing resistance of Candida species, it is necessary to explore alternative strategies. In this context, essential oils have emerged as promising options, among which the essential oil of Astronium urundeuva (M. Allemão) Engl. has shown potential, as it is traditionally used in folk medicine for the treatment of inflammation and multiple infections. Thus, the aim of this study was to evaluate the chemical profile, anti-Candida activity, and Fluconazole (FCZ) potentiating effect of the essential oil extracted from the leaves of A. urundeuva (EOAU) and its ability to inhibit the virulence mechanism in Candida species.

The essential oil was obtained via hydrodistillation and characterized using gas chromatography-mass spectrometry. To evaluate the antifungal effects and the modulating activity of Fluconazole (FCZ), the essential oil was diluted in DMSO (1 mL) and SDB medium (9 mL) and tested on 3 Candida strains using the serial microdilution method. In addition, a morphological transition assay was used to evaluate its capacity to inhibit fungal virulence.

The major constituent of EOAU was the monoterpene β-myrcene (71.07%). The results indicate that the essential oil exhibits an antifungal effect, with C. tropicalis being the most susceptible species. At subinhibitory concentrations (MC/8), the EOAU enhanced the action of fluconazole against C. krusei and C. tropicalis. The EOAU strongly inhibited the morphological transition in C. tropicalis.

EOAU is rich in β-myrcene and exhibits an interesting fungistatic effect, making it a great natural candidate for inhibiting Candida spp. virulence.

The crystallization of heme into β-hematin and its subsequent conversion to hemozoin has garnered significant interest as a promising target for the development of novel antimalarial therapies, particularly through the heme detoxification pathway. Furthermore, the therapeutic efficacy of chloroquine (CQ) has been widely recognized, with several studies highlighting its role as an inhibitor of β-hematin and hemozoin formation.

This study reports the synthesis of two novel CQ-derived compounds, 7-chloroquinolin-4-amine (CQC1) and 7-chloro-4-(¹-oxidaneyl)-3,4-dihydroquinoline (CQC2), and evaluates their individual inhibitory effects on β-hematin formation.

Notably, comparative analysis of the experimental data revealed significant variability in the IC50 values for these compounds, which correspond to the concentration required to inhibit 50% of β-hematin synthesis. The impact of incubation time and compound concentration on IC50 values was also investigated.

The findings suggest that increasing the concentration and incubation time of both CQ derivatives led to a reduction in their IC50 values, with both compounds demonstrating enhanced inhibitory activity relative to commercial chloroquine (CQ).

Bacterial cellulose, which is used in many fields from biomedicine to electronics, is promising as an alternative wound dressing instead of traditional gauze in wound treatment.

The objective of this study was to evaluate the potential use of cellulose produced by acetic acid bacteria isolated from rotten fruits as a wound dressing.

In our study, rotten fruit samples were incubated in Hestrin-Schramm (HS) Broth medium. Then, a loopful of the pellicle-forming samples was taken and inoculated onto Hestrin-Schramm (HS) agar using the streak culture method and bacteria were isolated. Identification of bacteria was performed using the BLAST program after 16S rRNA sequence analysis. Physicochemical properties and morphological characterization of bacterial cellulose produced by static culture were examined using Fourier transform infrared (FTIR) and scanning electron microscopy (SEM), respectively, and the swelling ratio was investigated. Antibiotic susceptibilities of bacterial cellulose membranes impregnated with different concentrations of gentamicin (50 µg/mL, 100 µg/mL, 200 µg/mL) against Staphylococcus aureus ATCC 29213 and Escherichia coli ATCC 25922 were determined by the disk diffusion method.

The bacteria isolated from rotten fruits were identified as Acetobacter tropicalis NBRC 16470. The structure of cellulose produced by static culture was confirmed by a peak at 3,240 cm⁻¹ in FTIR analysis and fibril structures in SEM analysis. Bacterial cellulose had a swelling ratio of 27.37± 2 .99 fold. The zone diameters formed by bacterial cellulose disk (50 µg/mL gentamicin) and gentamicin (10 µg) disk against Staphylococcus aureus ATCC 29213 and Escherichia coli ATCC 25922 were almost the same.

The production of bacterial cellulose, which has the potential to be used as a wound dressing from rotten fruits, is important in terms of recycling and low cost.

Scientists around the world are focusing on ‘green,’ environment-friendly, and cost-effective green synthesis of nanometals using various plant extracts to combat various ailments. Among nanometals, Silver (Ag) is one of the most commercialised nano-materials due to its wide applications in biotechnology and biomedical fields. The present study reports the first facile synthesis, characterization, and process optimisation of Ag nanoparticles (NPs) using aqueous Grewia tiliaefolia leaf extract (Gt) as a reducing and surface functionalising agent.

Characterisation of Gt-mediated Ag-NPs was performed using FTIR. The morphology and microstructures of Gt-derived Ag-NPs were analysed using TEM and FE-SEM. In vitro, antioxidant activity was evaluated against DPPH radicals, hydrogen peroxide radicals, and ferric ions. In vitro, anticancer activity was assessed on MCF-7 and HepG2 cell lines. In vivo, hepatoprotective activity was tested against paracetamol-induced liver toxicity in rats.

FTIR analysis confirmed the interaction between Ag-NPs and Gt. The optimal conditions for Gt-derived Ag-NPs were found to be 4 mM AgNO3, 5% Gt, at 90°C for 60 minutes, at pH 9. UV-Visible spectroscopy, XRD, FE-SEM, and TEM revealed the phase formation, spherical morphology, and surface functionalisation of Gt-derived Ag-NPs, which were stable (-28.3 mV) with an average particle size of 14.5±0.05 nm. The Gt-derived Ag-NPs were found to be highly effective in significantly inhibiting DPPH radical, ferric ions, and hydroxyl radicals. Additionally, the cytotoxicity of Gt-derived Ag-NPs was more effective against MCF-7 cells compared to HepG2 cells. They also exhibited dose-dependent protection against hepatoprotective activity in albino rats.

The hepatoprotective effects of Gt-mediated Ag-NPs likely result from the combined action of bioactive phytochemicals (such as α/β-amyrin, γ-lactones, betulin, and lupeol), and their ability to scavenge ROS, reduce oxidative stress, and modulate inflammatory pathways. These mechanisms, supported by reduced lipid peroxidation and increased antioxidant activity in paracetamol-induced hepatotoxicity, suggest their therapeutic potential in liver protection and regeneration.

Overall, Gt proves to be an eco-friendly and non-toxic source for synthesizing bioactive Ag-NPs at optimal conditions.

The combination of Gardeniae Fructus (ZZ) and Scutellariae Radix (HQ) is a traditional Chinese medicine used for Alzheimer’s disease (AD). However, the molecular mechanisms underlying its anti-dementia effects, particularly its multi-component synergy and pathway modulation, remain poorly understood.

Our study employed an integrated systems pharmacology approach to mechanistically decode the anti-AD properties of ZZ-HQ, combining network pharmacology predictions, molecular docking simulations, and experimental validation to identify critical bioactive components, molecular targets, and therapeutic pathways.

A comprehensive network pharmacology analysis was performed to identify bioactive compounds within the ZZ-HQ complex and their potential protein targets associated with AD. Molecular docking was utilized to predict and assess the binding interactions between key bioactive compounds and AD-related protein targets. Experimental validation focused on baicalin, a major active compound in the ZZ-HQ complex, evaluating its effects on cell viability, apoptosis regulation, oxidative stress reduction, and the activation of the PI3K/Akt signaling pathway.

Fifty-four bioactive compounds were identified in the ZZ-HQ complex, interacting with 258 AD-associated proteins. Key compounds, such as baicalein and norwogonin, demonstrated strong binding affinities with pivotal proteins, including SRC and PIK3R1. Experimental studies further confirmed that baicalin significantly improved cell viability by activating the PI3K/Akt pathway, reducing apoptosis, and alleviating oxidative stress.

Our study uncovered the therapeutic potential of the ZZ-HQ combination in addressing AD through multi-target mechanisms, particularly via modulation of the PI3K/Akt pathway and oxidative stress. These findings provide a scientific basis for the pharmacological effects of ZZ-HQ and offer valuable insights for further research on its potential application in AD treatment.

Hydroxysafflor Yellow A (HSYA), known for its anti-inflammatory effects in cardiovascular diseases, has also been shown to reduce adiposity and improve metabolic disorders in diet-induced obese (DIO) mice. However, the molecular mechanisms underlying its anti-obesity effects, particularly whether they are mediated through immune-inflammatory pathways, remain unclear. This study aims to identify the key molecular mechanisms involved in HSYA's anti-obesity action.

Male C57BL/6J mice were divided into three groups: Standard Feed (SF), High-Fat Diet (HFD), and HFD with HSYA treatment (250 mg/kg/day for 9 weeks). Whole transcriptome sequencing of White Adipose Tissue (WAT) identified Differentially Expressed Genes (DEGs), which were integrated with network pharmacology predictions to identify key molecular targets of HSYA. RT-qPCR in WAT, 3T3-L1 adipocytes, and RAW264.7 macrophages validated the core genes, and molecular docking assessed HSYA’s binding affinity with these targets.

HSYA treatment significantly reduced body weight (35.27 ± 1.27g vs. 45.46 ± 1.68g, p < 0.05) and WAT mass (3.38±0.21g vs. 1.86±0.27g, p < 0.05) in DIO mice and ameliorated glucose and lipid metabolism abnormalities. Transcriptome analysis revealed 739 DEGs, with 21 overlapping genes identified between sequencing and network pharmacology analyses. Experimental validation highlighted Prkcd, Btk, and Vav1 as core genes within immune-inflammatory pathways, including chemokine and B cell receptor signaling, which are implicated in obesity-related inflammation. RT-qPCR confirmed the downregulation of Prkcd, Btk, and Vav1 after HSYA treatment, consistent with transcriptomic findings. Molecular docking analysis demonstrated strong binding affinities between HSYA and VAV1 (-8.5 kcal/mol), BTK (-6.9 kcal/mol), and PRKCD (-6.6 kcal/mol).

HSYA demonstrates the therapeutic potential for obesity by modulating immune-inflammatory pathways in WAT, specifically targeting Prkcd, Btk, and Vav1 in mice. Given its clinical use in cardiovascular disease, these findings suggest that HSYA may offer broader therapeutic benefits, including obesity management, though further studies are needed to clarify the mechanisms and assess its applicability to humans.

This study investigates causal relationships between gut microbiota (GM), plasma metabolites, and cerebral small vessel disease (CSVD), with a focus on identifying GM taxa and metabolites that mediate disease risk.

Summary data from genome-wide association studies on GM (MiBioGen), 1,400 plasma metabolites, and CSVD were analyzed using a two-step Mendelian randomization (MR) approach. The primary analysis utilized inverse-variance weighting, complemented by weighted median, weighted mode, and MR-Egger methods for robustness.

The MR analysis identified 12 GM taxa associated with CSVD risk, including 7 taxa linked to increased risk (Veillonellaceae, Hungatella, Ruminococcus2, Lachnospiraceae UCG010, Streptococcus, Cyanobacteria, Verrucomicrobia) and 5 taxa linked to decreased risk (Faecalibacterium, Alphaproteobacteria, Eubacterium nodatum group, Fusicatenibacter, Rhodospirillales). Additionally, 10 plasma metabolites were causally associated with CSVD risk, with sphingomyelin (d18:2/14:0, d18:1/14:1), nicotinamide, 3-ethylcatechol sulfate (2), sphingosine, and phenylpyruvate-to-4 hydroxyphenylpyruvate ratio linked to increased risk, while phosphate-to-uridine ratio, adenosine 5'-diphosphate (ADP)-toflavin adenine dinucleotide (FAD) ratio, arginine, caffeine-to-theobromine ratio and N-succinylphenylalanine were linked to decreased risk. Mediation analysis identified 8 causal pathways through which plasma metabolites connect GM taxa to CSVD.

These findings underscore the substantial influence of GM and plasma metabolites on CSVD risk, highlighting potential therapeutic targets. Further investigation is needed to elucidate the biological mechanisms underlying these associations.

Drug and chemical nephrotoxicity is a common cause of kidney disorders. This systematic review aimed to evaluate the recent progress in applying nano-curcumins (nano-CURs) to prevent and mitigate drug and chemical-induced nephrotoxicity, highlighting their underlying protective mechanisms and therapeutic potential.

A comprehensive search of experimental and clinical studies was conducted in various databases, including Web of Science, PubMed/MEDLINE, Scopus, Embase, and Cochrane Library. The studies were analyzed for improvements in bioavailability, mechanisms of action, and outcomes in reducing kidney damage. After extracting the data and entering it into an Excel sheet, the essential information and the related knowledge on consequences and mechanisms were collected. The collected information was discussed and analyzed.

The antioxidant property of nano-CURs in dealing with nephrotoxicity is one of their most critical nephroprotective properties. They also exhibit potent anti-inflammatory, anti-apoptotic, and anti-pyroptotic effects. Moreover, nano-CURs improve mitochondrial function, modulate kidney biochemical markers, modulate electrolyte imbalance, reduce endoplasmic reticulum (ER) stress, and improve kidney histopathological changes and autophagy, offering protection against nephrotoxicity induced by various drugs and chemicals. Nano-CURs significantly improve histopathological changes. Animal models have demonstrated reduced oxidative stress, inflammation, and apoptosis, causing improved renal function and histological outcomes.

Nano-CURs have shown promising nephroprotective effects in experimental studies. However, these results have not been significant in clinical trial studies. Future research should focus on clinical trials and optimizing formulations for broader therapeutic applications.

Current medicine could benefit from gene and cell therapies for genetic defects, cancer, and degenerative disorders. These therapies modify genetic material or biological components. CRISPR-Cas9 gene editing, stem cell, and CAR-T treatments are examples. Complex products need rigorous regulations to ensure quality, efficacy, and patient safety.

This paper discusses international gene and cell-based treatment regulatory regimes, highlighting key issues and recent developments. It also includes gene and cell-based therapy classes and mechanisms.

The publications on gene and cell therapy challenges and their regulatory approvals in the US, Europe, Japan, Australia, Brazil, Canada, and China were collected over the last 20 years from PubMed, Scopus, and Google Scholar and analyzed to determine the differences.

Gene treatments correct genetic defects or disease processes by adding, removing, or changing cell genetic information. In contrast, cell-based therapies restore damaged tissues with modified or unmodified cells. Highly customized and patient-specific drugs make regulatory monitoring challenging. US FDA CBER controls gene and cell-based therapies. Before clinical trials, these biologic drugs must file BLAs for market approval and INDs.

FDA's Breakthrough Therapy and Regenerative Medicine Advanced Therapy (RMAT) designations accelerate biological development. The EMA oversees EU Advanced Therapy Medicinal Products. ATMP quality, safety, and efficacy are CAT's top priorities. The Conditional Marketing Authorization process expedites access to life-threatening disease medicines while the MAA regulates them. Japan's PMDA's Conditional Time-Limited Approval for regenerative medicines provides early commercialization and rigorous post-market supervision. Similarly, each country has adopted some ways to expedite the approval of biologicals. Gene-editing drugs require specialized methods, long-term follow-up, and better safety to avoid off-target effects. GMPs ensure production uniformity, sterility, and safety, complicating manufacturing and quality control.

The review concludes that there is a need for worldwide regulatory harmonization and regulatory framework developments, including R.W.E., adaptive pathways, and personalization of biologics.

Metabolic syndrome encompasses conditions such as diabetes mellitus (DM), which has become increasingly prevalent. Chemically synthesized medications are commonly used to mitigate the effects of DM and its complications; however, these often result in undesirable side effects, including weight gain, digestive issues, and heart failure.

This review highlights the therapeutic potential of bioactive compounds and anti-diabetic plants that possess proven anti-diabetic properties. Focusing on phytomedicines also explores their possible mechanisms of action and positions this work relative to current reviews in the field.

A comprehensive literature analysis was conducted, emphasizing the therapeutic potential of bioactive compounds in anti-diabetic plants. Databases such as PubMed, Scopus, and Google Scholar were thoroughly searched to identify studies investigating the anti-diabetic properties and mechanisms of action of plant-derived bioactive compounds. Inclusion criteria focused on studies evaluating the pharmacological effects of herbal medicines, plant extracts, and isolated bioactive compounds on diabetes management.

Therapeutic plants, as sources of anti-diabetic compounds, offer significant advantages. They are affordable, exhibit minimal or no adverse effects, and do not necessitate strict dietary restrictions or intense exercise regimens. The integrated insights underscore the potential of phytomedicines to address limitations in current diabetes management strategies.

The unique focus on phytomedicines positions this review as a valuable resource for researchers and clinicians. Detailing mechanisms and evidence supporting the efficacy of these compounds, guides the development of innovative strategies for identifying and utilizing bioactive compounds in effective diabetes management.

Bibliometrics has been applied to the study of tumor image segmentation, which can indicate the current research hotspots and trends.

In this study, bibliometric analyses were performed on data retrieved from the Web of Science database. A total of 3,377 articles on the application of tumor image segmentation from January 1, 2003, to October 9, 2024, were analyzed for the characteristics of the articles, including the number of yearly publications, country/region, institution, journal, author, keywords, and references. Visualising co-authorship, co-citation, and co-occurrence analysis with VOSviewer.

The annual publication volume of tumor image segmentation literature shows that from the first time of more than 100 articles in 2016, the publication volume of literature in this field has surged, reaching 576 articles by 2023. Mainland China is ranked first in terms of publication volume (n=1,356). Saudi Arabia ranks first in average publication year (n=2021.96). IEEE Transactions on Medical Imaging was the journal with the highest average number of citations. The Chinese Academy of Sciences (n=78) was the most prolific institution, while Harvard University was the most prestigious, with a total number of citations and an average number of citations of 3,190 and 213, respectively. In terms of keywords, co-occurrence analysis of 107 keywords with a frequency of more than 30 times produced four clusters: (1) methods of image segmentation, (2) applications of image segmentation, (3) image segmentation modelled on CT, (4) image segmentation modelled on MRI. Transformer, Attention Mechanism, and U-Net are the latest keywords. The analysis of keywords helps scholars understand and identify the current research hotspots and research directions.

Within the last 20 years, the number of articles on the application of tumor image segmentation has increased steadily. From U-Net to MAMBA, many methods for tumor image segmentation have been proposed, and the limitations of models and algorithms are becoming increasingly smaller, which demonstrates the importance of advances in tumor image segmentation technology for disease prevention and monitoring. It presents a strong connection between countries/regions and authors, which reflects the global interest and labelport for the development of this field. This study shows global trends, research hotspots, and emerging topics in this field and reviews some of the knowledge about tumor image segmentation applications from past studies. And it will provide good research guidelines for researchers in this field.

T-cell exhaustion (TEX) is one reason for immunotherapy resistance among cancers, but the specific mechanism and influencing factors of TEX in diffuse large B-cell lymphoma (DLBCL) are not fully understood. This study aimed to establish a TEX signature for predicting the prognosis of DLBCL and investigate the immune characteristics related to the TEX signature.

The gene expression data of DLBCL were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. Prognostic TEX related genes were selected by Cox regression analysis for prognostic signature (TEX score) construction. The correlation of risk grouping with immune cell infiltration was analyzed by CIBERSORT and ssGSEA. Molecular mechanisms between high and low TEX score groups were explored by gene set enrichment analysis (GSEA).

A total of 115 differentially expressed TEX-related genes were selected, and 12 were prognosis-related after Cox regression. Following Ninesignature genes, including TRIM6, BIRC3, CTSC, GBP3, IRF3, TRIM22, IFI30, TRIM25 and BAG4 were identified to construct a TEX score. The receiver operator characteristic curve curves suggested that the model presented high predictive precision. A nomogram was established, which also had good prediction performance in survival prognosis. The composition of immune cells in the two risk groups was significantly different. GSEA identified 33 hallmarks between two risk groups, which were associated with immune cells infiltration and inflammation.

The TEX score has prognosis-predicting value for DLBCL and might be a valuable biomarker to guide clinical decision‐making for patients with DLBCL.

Diet-related chronic diseases, such as cardiovascular diseases, obesity, diabetes, autoimmune diseases and cancer, are largely preventable with a healthy diet and lifestyle. Therefore, searching for dietary supplements rich in antioxidant and anti-inflammatory phytochemicals for the prevention and/or management of diet-related chronic diseases is an important strategy for controlling these diseases to reduce healthcare costs and sustain development.

The aim of the current research was to prepare dietary supplements from avocado fruit pulp [AFPDS] and evaluate their potential against various diet-related chronic diseases through in-vitro , in-vivo , and molecular docking studies.

Volatile compounds of avocado pulp were evaluated, and the total phenolic compounds, fatty acids, and phytosterols profiles of the AFPDS were determined.

D-limonene, methyl propanoate, isobutyl propanoate and pentanol were the principal volatile compounds in the avocado pulp. Total phenolic and flavonoids were present in the AFPDS by 9.65 mg GAE/g and 6.87 mg CE/g, respectively. Chlorogenic acid and cinnamic acid were the major and minor identified phenolic compounds in AFPDS, respectively. Oleic acid [75.06%] and β-Sitosterol [2.19%] were the highest fatty acid and phytosterol present in AFPDS, respectively. AFPDS recorded anti-inflammatory activity against nitric oxide [NO] production in RAW264.7 macrophages by 98.2µg/ml [IC50] and 164.8µg/ml [IC90]. AFPDS showed significant anti-inflammatory activity against carrageenan-induced rat paw edema. AFPDS showed antioxidant activity against DPPH and ABTS by 8.67 mg TE/g and 6.14 mg TE/g. AFPDS possessed anti-cancer activity against MCF7 and HPG2 at10.8µg/ml and 40.5µg/ml, respectively. AFPDS exhibited anti-diabetic activity as an inhibitor of α-amylase and α-glucosidase by26.35±0.77μg/ml and 0.55±0.163mg/ml, respectively. Molecular docking studies revealed high binding affinity of different active compounds present in AFPDS with cyclooxygenase-2, glutathione peroxidase, α-glucosidase and B-cell lymphoma-extra-large proteins.

AFPDS can be considered a new agent for the prevention and treatment of diet-related chronic diseases, such as diabetes and cancer, due to its anti-inflammatory, antioxidant, anticancer, and anti-diabetic activities, as demonstrated through in-vivo , in-vitro , and molecular docking studies.

Atherosclerosis (AS) is caused by the endothelium injury associated with oxidative stress. Previous studies have shown that the Phlegm-Eliminating and Stasis-Transforming Decoction (Huayu Qutan Decoction, HYQTD) has mitochondrial protective function. The objective of this research was to explore how HYQTD drug-containing serum (HYQTD-DS) could potentially protect mitochondrial energy production in endothelial cells (ECs) from injury caused by hydrogen peroxide (H2O2)-induced oxidative damage in AS through SIRT1/PGC-1α/ Nrf2 pathway.

After preparation of containing serum, the cells were divided into various categories, such as control group, H2O2 group (an oxidative damage model), HYQTD group, Selisistat (EX527, a SIRT1 inhibitor) combined with H2O2 group, and EX527 combined with HYQTD group. The evaluation of oxidative stress involved measuring reactive oxygen species (ROS) and malondialdehyde (MDA) generation, as well as Superoxide Dismutase (SOD) activity. Mitochondrial function and ultrastructure were measured by Transmission electron microscopy (TEM), mitochondrial membrane potential (MMP), rate of oxygen consumption (OCR), respiratory chain complex activities, and ATP production. The key proteins and gene levels in the SIRT1/PGC-1α/Nrf2 pathway was quantified by quantitative real-time PCR (RT-PCR) and Western blotting analysis.

We found oxidative stress, mitochondrial damage, and mitochondrial energy disorder in H2O2-induced ECs. However it indicated a marked reversal after pretreated with HYQTD-DS. Mechanistically, EX527 induced increased oxidative stress, worse mitochondrial dysfunction, and less ATP synthesis.

We demonstrated that HYQTD-DS attenuated oxidative stress, improved mitochondrial function, and up-regulated mitochondrial ATP synthesis by activating SIRT1/PGC-1α/Nrf2 pathway-induced mitochondrial biogenesis and its downstream NADH dehydrogenase (ubiquinone) flavoprotein 2 (NDV2).

This study evaluated the renoprotective effects of p-Coumaric acid nanoparticles (PCNPs) in nephropathic rats.

Six groups of male Albino Wistar rats were randomly assigned. Group 1 was the control, while Group 2 received 45 mg/kg of streptozotocin (STZ) to induce diabetic nephropathy. Groups 3, 4, and 5 received STZ (45 mg/kg) along with PCNPs at doses of 20, 40, and 80 mg/kg, respectively. Group 6 received 80 mg/kg of PCNPs without STZ. Body weight, blood glucose, insulin, hemoglobin (Hb), and glycosylated hemoglobin (HbA1c) levels were measured. Blood urea, serum creatinine, kidney antioxidant enzymes, and lipid peroxidation levels were also analyzed. Histological and immunohistochemical studies of kidney tissues were performed.

PCNPs (80 mg/kg) significantly reduced serum glucose, creatinine, and urea levels while increasing insulin levels and antioxidant activity in the kidneys. Histological analysis revealed that nephropathic rats exhibited cellular damage, including shrinkage of Bowman’s capsule and lesions in the kidneys, along with degeneration in the Islets of Langerhans in the pancreas. PCNPs treatment restored these morphological alterations in the pancreas, liver, and kidneys to near-normal. Furthermore, nephropathic rats had elevated IL-6 and TNF-α expression in the renal tubules and glomeruli, which was reduced following PCNPs treatment.

The findings suggest that PCNPs exhibit antihyperglycemic, antioxidant, anti-glycation, and renoprotective effects in STZ-induced diabetic nephropathy.

Prostate cancer is an androgen-dependent malignancy, and the use of androgen deprivation therapies frequently results in treatment resistance, relapse, and the development of aggressive castration-resistant tumors. Patchouli alcohol, a tricyclic sesquiterpene derived from Pogostemon cablin of the Labiatae family, has demonstrated potential in modulating inflammatory responses and tumor progression. This study aimed to investigate the mechanisms through which patchouli alcohol influences inflammatory pathways associated with prostate cancer using bioinformatics and experimental validation.

Differentially Expressed Genes (DEGs) were identified from the GSE46602 dataset, containing 36 prostate cancer and 14 normal prostate biopsy samples, using the GEO2R tool (adjusted P < 0.05). Functional annotation was performed using GO and KEGG databases, while PPI networks were constructed via STRING and Cytoscape. Key hub genes were identified. To validate the bioinformatics findings, qPCR and Western blotting were employed to confirm the differential expression of selected hub genes in DU145 prostate cancer cells treated with patchouli oil.

Bioinformatic analysis revealed 71 DEGs, including 35 upregulated and 36 downregulated genes. Thirteen hub genes were identified (DCK, APRT, ADK, KCNK9, ADSL, PKM, KCNK3, S100A10, ENTPD2, PKLR, ARHGEF38, TPK1, and AK5), which were enriched in pathways, such as MAPK, PI3K-Akt, Ras, and Rap1. Experimental validation confirmed the upregulation of DCK, APRT, KCNK9, ADSL, PKM, S100A10, ENTPD2, PKLR, ARHGEF38, and AK5, and the downregulation of ADK, KCNK3, and TPK1 at both the mRNA and protein levels.

Patchouli alcohol appears to influence multiple hub genes associated with prostate cancer progression through its modulation of key cellular signaling and metabolic pathways. These findings support its potential role as a therapeutic agent for prostate cancer.

This study aimed to comprehensively investigate the molecular landscape of gastric cancer (GC) by integrating various bioinformatics tools and experimental validations.

GSE79973 dataset, limma package, STRING, UALCAN, GEPIA, OncoDB, cBioPortal, DAVID, TISIDB, Gene Set Cancer Analysis (GSCA), tissue samples, RT-qPCR, and cell proliferation assay were employed in this study.

Analysis of the GSE79973 dataset identified 300 differentially expressed genes (DEGs), from which COL1A1, COL1A2, CHN1, and FN1 emerged as pivotal hub genes using protein-protein interaction network analysis. Subsequent validation across The Cancer Genome Atlas (TCGA) datasets confirmed their up-regulation in GC tissues compared to normal controls. Promoter methylation analysis revealed decreased methylation levels of these hubs in GC tissues, suggesting their potential role in tumorigenesis. Mutational analysis using cBioPortal showcased frequent mutations in these genes, particularly FN1, further highlighting their significance in GC pathogenesis. Survival analysis indicated their correlation with reduced overall survival rates among GC patients, supported by the development of a robust prognostic model. Prediction of hub-associated miRNAs and gene enrichment analysis provided insights into their regulatory mechanisms and downstream pathways, implicating their involvement in extracellular matrix remodeling and cell migration. Drug sensitivity analysis revealed correlations between hub gene expression and drug response, while RT-qPCR validation confirmed their up-regulation in clinical GC samples. Finally, functional assays demonstrated the impact of FN1 knockdown on cellular proliferation, colony formation, and wound healing capacities.

Overall, this study elucidates the crucial role of COL1A1, COL1A2, CHN1, and FN1 in GC pathogenesis and underscores their potential as diagnostic markers and therapeutic targets.

Iron oxide nanozyme was synthesized from the fruit peel extract of pomegranate, which served as a reducing agent during the green synthesis. The scavenging of reactive oxygen species is often accompanied by immunomodulation following antiproliferative effects due to the crosstalk between the proteins involved in the inter-related signaling pathways.

In the current study, the green synthesized nanozyme was studied for its ability to induce apoptosis in breast cancer cell lines. The free radical scavenging effect of the nanozyme was reflected as an extension of its intrinsic endogenous enzyme-mimicking property.

The cell cycle analysis revealed that the cell death induced by nanozyme mainly affected the G0/G1 phase. The expression of RelA/p65 and the inflammatory mediators affected by the nanozyme established the role of the Fe3O4 nanozyme in immunomodulation along with its antiproliferative activity.

This is the first report on the antiproliferative and immunomodulatory activities expressed by the biomimetic iron oxide nanozyme.

The increasing prevalence of antibiotic-resistant bacteria necessitates exploring nanotechnology as a potential solution for microbial elimination.

This study aimed to investigate the antimicrobial and antioxidant effects of silver nanoparticles synthesized using aqueous extract from the Ephedra gerardiana (E. gerardiana) plant (EG@AgNPs).

Optimal synthesis conditions, including silver nitrate concentration, time, and temperature, were determined. Characterization of EG@AgNPs was conducted, which was followed by antimicrobial assessment against eight bacterial strains and one fungal strain. Additionally, the antioxidant properties of EG@AgNPs were evaluated using the DPPH method.

XRD analysis confirmed EG@AgNPs synthesis. DLS analysis revealed a hydrodynamic diameter of 22 nm. FT-IR analysis confirmed the presence of functional groups from the E. gerardiana plant extract in EG@AgNPs. FESEM and TEM images depicted spherical nanoparticles ranging in size from 10 to 20 nm. Antimicrobial investigations using the broth microdilution method demonstrated that E. gerardiana plant extract at 7.5 mg/ml inhibited only Streptococcus mutans and Candida albicans growth, with no antimicrobial effects observed at lower concentrations. However, EG@AgNPs significantly enhanced the antimicrobial properties of the E. gerardiana plant extract. Notably, these nanoparticles exhibited the most significant effect on E. coli and the least on S. salivaris, with MIC value of 125 and 2000 µg/ml, respectively. Furthermore, they inhibited C. albicans growth at a concentration of 62.5 μg/ml. An assessment of the antioxidant properties of EG@AgNPs indicated a significant increase in antioxidant activity.

The E. gerardiana plant extract has emerged as a promising option for silver nanoparticle synthesis. These nanoparticles have been found to exhibit potent antimicrobial properties against Gram-positive and Gram-negative bacterial species, as well as C. albicans. Additionally, they have demonstrated antioxidant properties.

This study aimed to explore the effects of Jiangu Recipe (JGR) on chondrocyte responses under tert-Butyl hydroperoxide (TBHP)-induced oxidative stress, specifically focusing on apoptosis and extracellular matrix (ECM) degradation.

Chondrocytes were treated with varying JGR concentrations, and cell viability was assessed. The impact of JGR on TBHP-induced apoptosis and protein expression levels of apoptosis-related molecules (Bcl-2, Bax, and cleaved caspase-3) and ECM components (Collagen II, Aggrecan, MMP-13) was evaluated.

JGR exhibited protective effects against oxidative stress in chondrocytes. Moreover, it maintained cell viability under tert-butyl hydroperoxide (TBHP) induction, suppressing apoptosis (Bax, cleaved caspase-3) and enhancing anti-apoptotic Bcl-2. JGR also attenuated extracellular matrix (ECM) degradation, promoting Collagen II and Aggrecan while reducing MMP-13 expression. Investigating endoplasmic reticulum (ER) stress, it was found that JGR downregulated TBHP-induced GRP78, CHOP, ATF4, p-PERK, and p-eIF2α, thus indicating ER stress modulation. SIRT1 played a key role, as JGR upregulated SIRT1, mitigating TBHP-induced downregulation. SIRT1 knockdown reversed JGR's protective effects, highlighting its crucial role in JGR-mediated responses.

Our findings suggest that JGR mitigated TBHP-induced chondrocyte apoptosis and ECM degradation, highlighting its potential therapeutic application in osteoarthritis. Mechanistically, our study highlights that SIRT1 plays a crucial role in mediating the protective effects of JGR against ER stress-induced chondrocyte apoptosis and ECM degradation, providing a foundation for further clinical exploration in managing osteoarthritic conditions.